This study was designed to test the hypothesis that young animals with vesicoureteral reflux might be more vulnerable to renal parenchymal infection by bacteria to which they had not been previously exposed. Forty-four crossbred male piglets had surgical induction of vesicoureteral reflux at 2 weeks of age and introduction of urinary tract infection at 6 weeks. They were sacrificed at 12 weeks of age. Between the ages of 2 and 6 weeks, 22 piglets received subcutaneous injections of formalin-killed Escherichia coli in incomplete Freund's adjuvant as described. The remaining 22 piglets received incomplete Freund's adjuvant and vehicle alone. The antibody responses to antigenic challenge were weak to moderate. Immunized animals tended to have less renal scarring and better renal tubular uptake of dimercaptosuccinic acid, in addition to significantly lower serum creatinine values (p less than 0.001) and less mesangial cell proliferation in glomeruli (p = 0.05). We conclude that previous exposure to a specific bacterial strain and bacterial immunization have at least a mild protective effect on the development of reflux nephropathy.